CN101200420A - Method for preparing 4'-hydroxy-2,4,6-trimethoxy dihydrocharcone - Google Patents
Method for preparing 4'-hydroxy-2,4,6-trimethoxy dihydrocharcone Download PDFInfo
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- CN101200420A CN101200420A CNA2007100479124A CN200710047912A CN101200420A CN 101200420 A CN101200420 A CN 101200420A CN A2007100479124 A CNA2007100479124 A CN A2007100479124A CN 200710047912 A CN200710047912 A CN 200710047912A CN 101200420 A CN101200420 A CN 101200420A
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- trimethoxy
- benzyloxy
- dihydrochalcone
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
The invention relates to a method of the preparation of loureirin B i.e. 4' -hydrox-2, 6-trimethoxychalcone, pertaining to the technical field of the chemical synthesis of dihydrochalcone. The invention takes 4-benzyloxy acetophenone as raw material to conduct aldol condensation reaction with 2, 4, 6-trimethoxybenzaldehyde in alkaline alcohol solution to achieve intermediate 4'- benzyloxy-2, 4, 6- trimethoxychalcone; subsequently, the intermediate is added with hydrogen for reduction under the existence of catalyst Pd/C, and de-protecting group, and finally, the desired loureirin B is achieved. The invention provides a method for the chemical synthesis of loureirin B, the operation method is simple and safe, the achieved product has high purity and has activity as high as that of the loureirin B extracted from Longxuejie (Chinese medicine).
Description
Technical field
The present invention relates to the i.e. 4 '-hydroxyl-2,4 of a kind of lourerin B, the preparation method of 6-trimethoxy dihydrochalcone.Belong to dihydrochalcone organic chemistry synthesis technology field.
Background technology
Lourerin B (4 '-hydroxyl-2,4,6-trimethoxy dihydrochalcone) is a kind of dihydrochalcone that separation and Extraction obtains from the Chinese medicine Sanguis Draxonis.Dihydrochalcone is the very important activeconstituents of a class, has anti-oxidant, antitumor, anti-diabetic, antibiotic and estrogen-like effects.Lourerin B now has been used to one of reference material in the quality control of Chinese medicine Sanguis Draxonis.Now, prove that it has good function of promoting blood circulation to disperse blood clots by the external activity experiment.The purposes of this product is wide, and good market outlook are arranged.
Its structural formula is as follows:
Pertinent literature by retrieval: only find once to synthesize similar precursor structure (Phytochemistry, 27 (6), 1835-1841,1988) at present abroad.
In above-mentioned document, once be reported in room temperature and carried out aldol reaction 24 hours, after the reaction, carry out purifying with the chromatographic column separation.Generate dihydrochalcone with Zn as the reductive catalyzer.In above-mentioned method, long reaction time, the product demand pole that obtains separates, and is consuming time, complex operation.As the reductive catalyzer, aftertreatment bothers with Zn.
Do not see the report of synthetic lourerin B both at home and abroad as yet.
Summary of the invention
The purpose of this invention is to provide the i.e. 4 '-hydroxyl-2,4 of a kind of lourerin B, the synthetic method of 6-trimethoxy dihydrochalcone, the shortcoming of few, consuming time, the consumption power of yield, consumption natural resource when overcoming from Chinese medicine Sanguis Draxonis separation and Extraction.
Technical conceive of the present invention is such: with 4-benzyloxy methyl phenyl ketone is raw material; then under the effect of potassium hydroxide alcoholic solution with 2; 4; the 6-TMB is carried out aldol condensation; the intermediate that obtains reduces in the presence of catalyzer and the deprotection group, obtains target product lourerin B of the present invention.Its reaction is as follows:
Raw material 4-benzyloxy methyl phenyl ketone used in the present invention is reference literature Synthesis and anticanceractivity of benzyloxybenzaldehyde derivatives against HL-60 cells.LinChin-Fen; Yang Jai-Sing; Et al., Bioorganic ﹠amp; Medicinal Chemistry (2005), 13 (5), reported method synthetic among the 1537-1544..
The present invention's a kind of 4 '-hydroxyl-2,4, the preparation method of 6-trimethoxy dihydrochalcone is characterized in that having following process and step:
A. be raw material with 4-benzyloxy methyl phenyl ketone, under nitrogen protection in alkali alcosol with 2,4, the 6-TMB is carried out aldol reaction, and temperature of reaction is 60 ~ 100 ℃, and the time is 3 ~ 16 hours, reaction finishes, the 4 '-benzyloxy that obtains after filtration-2,4,6-trimethoxy phenyl styryl ketone intermediate, raw material 4-benzyloxy methyl phenyl ketone and 2,4, the consumption of 6-TMB, promptly both quality mol ratios are 1: 1 ~ 1: 1.2;
B. with the intermediate 4 '-benzyloxy-2,4 of above-mentioned gained, 6-trimethoxy phenyl styryl ketone is put in the alkali alcosol, is reducing and the deprotection group in the presence of the Pd/C catalyzer and under the hydroconversion condition.The temperature of reduction reaction is 25 ~ 40 ℃, and the time is 2 ~ 8 hours, and reaction finishes, and after filtration, gets crude product, and is final that the target product lourerin B is 4 '-hydroxyl-2,4 again through ethyl alcohol recrystallization, 6-trimethoxy dihydrochalcone.
Above-mentioned alkali alcosol is any the formulated alkali alcosol that has in any and methyl alcohol in sodium hydroxide, potassium hydroxide, yellow soda ash, the salt of wormwood, ethanol, propyl alcohol, the Virahol, alkali is 1: 5 ~ 1: 10 with the weightmeasurement ratio of alcohol, promptly in the ratio preparation alkali alcosol of per 1 gram alkali with 5 ~ 10 milliliters alcohol.
The above-mentioned raw material 4-benzyloxy methyl phenyl ketone and the mass volume ratio of solvent alcohol are 1: 20 ~ 1: 50, promptly come obtain solution in per 1 gram raw material with the ratio of 20 ~ 50 milliliters of alcohol.
In above-mentioned hydrogenation reduction, its composition proportioning of described Pd/C catalyzer is 2%, 5% and 10%, use wherein any, catalyst consumption is according to intermediate 4 '-benzyloxy-2,4, the consumption of 6-trimethoxy phenyl styryl ketone and deciding, 4 '-benzyloxy-2,4, the mass ratio of 6-trimethoxy phenyl styryl ketone and Pd/C catalyst levels is 1: 0.5 ~ 1: 2, and described hydroconversion condition remains 5 ~ 15mmHg for the pressure that feeds hydrogen.
Concrete real-time mode
After now specific embodiments of the invention being described in.
Embodiment 1
At N
2In the there-necked flask of protection, add 2.26g (0.01mol) 4-benzyloxy methyl phenyl ketone, 1.96g (0.01mol) 2,4, the 6-TMB under agitation adds the solution that is made into by 83mL propyl alcohol and 9.3g (0.16mol) KOH.Finish post-heating and reflux, follow the tracks of reaction with TLC, raw material point disappeared in 3 hours.Separate out a large amount of yellow solid matter in the reaction process gradually, leach this yellow solid after reaction finishes, i.e. 4 '-benzyloxy-2,4,6-trimethoxy phenyl styryl ketone, dry 3.5g, obtain yellow needle-like crystal 3.2g with the 50mL ethyl alcohol recrystallization.Detecting purity with high performance liquid chromatography is 99%; Yield: 80%.
In there-necked flask (band mercury seal), add 1.2g (2.97mmol) 4 '-benzyloxy-2,4,6-trimethoxy phenyl styryl ketone, the 150mL dissolve with ethanol adds 11.88mL 1mol/L KOH solution, 0.8g 10%Pd/C catalyzer.The room temperature lower magnetic force stirs, and feeds hydrogen with the hydrogen bag.Sealing system, the control intake valve makes mercury column keep 10mmHg.When the mercury column in the mercury seal kept 30min no longer to become, stopped reaction filtered and removes catalyzer.The rotary evaporation solvent gets crude product 0.83g, uses the 10mL ethyl alcohol recrystallization.Obtain pale yellow crystals 0.8g.Fusing point: 132.2-133 ℃.The parameters of fusing point and structure elucidation UV-VIS, IR, NMR, MS is all consistent with the literature value of the lourerin B that extracts from Sanguis Draxonis.Detecting purity with high performance liquid chromatography is 99.2%, yield: 85%.
Embodiment 2
At N
2In the there-necked flask of protection, add 2.26g (0.01mol) 4-benzyloxy methyl phenyl ketone, 2.15g (0.011mol) 2,4, the 6-TMB under agitation adds the solution that is made into by 50mL ethanol and 5.6g (0.1mol) KOH.Finish post-heating and reflux, follow the tracks of reaction with TLC, raw material point disappeared in 6 hours.Separate out a large amount of yellow solid matter in the reaction process gradually, leach this yellow solid after reaction finishes, be 4 '-benzyloxy-2,4,6-trimethoxy phenyl styryl ketone, dry 3.4g, obtain yellow needle-like crystal 3.1g with the 50mL ethyl alcohol recrystallization.HPLC: detecting purity with high performance liquid chromatography is 99.3%, yield: 76.7%.
In there-necked flask (band mercury seal), add 1.2g (2.97mmol) 4 '-benzyloxy-2,4,6-trimethoxy phenyl styryl ketone, the 100mL dissolve with ethanol adds 11.8mL lmol/L NaOH solution, 2g 5%Pd/C catalyzer.The room temperature lower magnetic force stirs, and feeds hydrogen with the hydrogen bag.Sealing system, the control intake valve makes mercury column keep 15mmHg.When the mercury column in the mercury seal kept 30min no longer to become, stopped reaction filtered and removes catalyzer.The rotary evaporation solvent gets crude product 0.8g, uses the 10mL ethyl alcohol recrystallization.Obtain pale yellow crystals 0.75g.Fusing point: 132.1-132.8 ℃.The parameters of fusing point and structure elucidation UV-VIS, IR, NMR, MS is all consistent with the literature value of the lourerin B that extracts from Sanguis Draxonis.Detecting purity with high performance liquid chromatography is 99%, yield: 80%.
Embodiment 3
At N
2In the there-necked flask of protection, add 2.26g (0.01mol) 4-benzyloxy methyl phenyl ketone, 2.35g (0.012mol) 2,4, the 6-TMB under agitation adds the solution that is made into by 100mL ethanol and 16.8g (0.3mol) KOH.Finish post-heating to 60 ℃, follow the tracks of reaction, raw material point disappearance in 15 hours with TLC.Separate out a large amount of yellow solid matter in the reaction process gradually, leach this yellow solid after reaction finishes, i.e. 4 '-benzyloxy-2,4,6-trimethoxy phenyl styryl ketone, dry 3.3g, obtain yellow needle-like crystal 3.15g with the 50mL ethyl alcohol recrystallization.Detecting purity with high performance liquid chromatography is 99%, yield: 78%.
In there-necked flask (band mercury seal), add 1.2g (2.97mmol) 4 '-benzyloxy-2,4,6-trimethoxy phenyl styryl ketone, the 100mL dissolve with ethanol adds 18.88mL 1mol/L NaOH solution, 0.8g 10%Pd/C catalyzer.The room temperature lower magnetic force stirs, and feeds hydrogen with the hydrogen bag.Sealing system, the control intake valve makes mercury column keep 5mmHg.When the mercury column in the mercury seal kept 30min no longer to become, stopped reaction filtered and removes catalyzer.The rotary evaporation solvent gets crude product 0.81g, uses the 10mL ethyl alcohol recrystallization.Obtain pale yellow crystals 0.73g.The parameters of fusing point: 132.6-133.4 ℃ fusing point and structure elucidation UV-VIS, IR, NMR, MS is all consistent with the literature value of the lourerin B that extracts from Sanguis Draxonis.Detecting purity with high performance liquid chromatography is 98.8%, yield: 78%.
Claims (4)
1. 4 '-hydroxyl-2,4, the preparation method of 6-trimethoxy dihydrochalcone is characterized in that having following process and step:
A. be raw material with 4-benzyloxy methyl phenyl ketone, under nitrogen protection in alkali alcosol with 2,4, the 6-TMB is carried out aldol reaction, and temperature of reaction is 60 ~ 100 ℃, and the time is 3 ~ 16 hours, reaction finishes, obtain 4 '-benzyloxy-2,4 after filtration, 6-trimethoxy phenyl styryl ketone intermediate, raw material 4-benzyloxy methyl phenyl ketone and 2,4, the consumption of 6-TMB, promptly both quality mol ratios are 1: 1 ~ 1: 1.2;
B. with the intermediate 4 '-benzyloxy-2,4 of above-mentioned gained, 6-trimethoxy phenyl styryl ketone is put in the alkali alcosol; reduction and deprotection group under hydroconversion condition in the presence of the Pd/C catalyzer; the temperature of reduction reaction is 25 ~ 40 ℃, and the time is 2 ~ 8 hours, and reaction finishes; after filtration; get crude product, again through ethyl alcohol recrystallization, final that the target product lourerin B is 4 '-hydroxyl-2; 4,6-trimethoxy dihydrochalcone.
2. a kind of 4 '-hydroxyl-2 as claimed in claim 1,4, the preparation method of 6-trimethoxy dihydrochalcone, it is characterized in that: described alkali alcosol is for by any the formulated alkali alcosol in any and methyl alcohol in sodium hydroxide, potassium hydroxide, yellow soda ash, the salt of wormwood, ethanol, propyl alcohol, the Virahol, alkali is 1: 5 ~ 1: 10 with the weightmeasurement ratio of alcohol, promptly prepares alkali alcosol in per 1 gram alkali with the ratio of 5 ~ 10 milliliters alcohol.
3. a kind of 4 '-hydroxyl-2 as claimed in claim 1,4, the preparation method of 6-trimethoxy dihydrochalcone, it is characterized in that: the mass volume ratio of described raw material 4-benzyloxy methyl phenyl ketone and solvent alcohol is 1: 20 ~ 1: 50, promptly comes obtain solution in per 1 gram raw material with the ratio of 30 ~ 100 milliliters of alcohol.
4. a kind of 4 '-hydroxyl-2 as claimed in claim 1,4, the preparation method of 6-trimethoxy dihydrochalcone, it is characterized in that: in described hydrogenation reduction, its composition proportioning of described Pd/C catalyzer is 2%, 5% and 10%, use wherein any, catalyst consumption is according to intermediate 4 '-benzyloxy-2,4, the consumption of 6-trimethoxy phenyl styryl ketone and decide 4 '-benzyloxy-2,4, the mass ratio of 6-trimethoxy phenyl styryl ketone and Pd/C catalyst levels is 1: 0.5 ~ 1: 2, and used hydroconversion condition remains 5 ~ 15mmHg for the pressure that feeds hydrogen.
Priority Applications (1)
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| CNA2007100479124A CN101200420A (en) | 2007-11-07 | 2007-11-07 | Method for preparing 4'-hydroxy-2,4,6-trimethoxy dihydrocharcone |
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| CNA2007100479124A CN101200420A (en) | 2007-11-07 | 2007-11-07 | Method for preparing 4'-hydroxy-2,4,6-trimethoxy dihydrocharcone |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382730A (en) * | 2017-06-30 | 2017-11-24 | 博润成（武汉）医药有限责任公司 | A kind of derivative of lourerin B and its preparation and application |
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- 2007-11-07 CN CNA2007100479124A patent/CN101200420A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107382730A (en) * | 2017-06-30 | 2017-11-24 | 博润成（武汉）医药有限责任公司 | A kind of derivative of lourerin B and its preparation and application |
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Open date: 20080618 |